Isolation of cDNA encoding a novel human CC chemokine NCC-4/LEC

Shoudai, Kiyomitsu; Hieshima, Kunio; Fukuda, Sachiyo; M, Iio; Miura, Retsu; Imai, Toshio; Yoshie, Osamu; Nomiyama, Hisayuki

doi:10.1016/s0167-4781(97)00235-2

Cited by 30 publications

(23 citation statements)

References 19 publications

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“…Vaccination with tumor cells transfected with MHC class II and B7.1 without removal of the primary tumor reduced the number of metastases, but had no impact on survival (28). Also, treatment with an immunostimulator as mB7-2 Ig fusion protein combined with the angiogenesis inhibitor SU668 started as earlier as 3 days after tumor injection significantly reduced tumor growth and number of lung metastases, but did not achieve a cure (57).…”

Section: Discussionmentioning

confidence: 99%

“…A critical issue is the size of the tumor at the time of vaccination, as tumors Ͼ4 mm in diameter already have a large metastatic load, precluding successful treatment (28). Surgical removal of the primary tumor as the first line of treatment in the 4T1 model was not sufficient to arrest metastases-induced death, but did change the setting in which a vaccine is called to act against residual disease (numerous small metastases).…”

Section: Discussionmentioning

confidence: 99%

“…Human CCL16 is a member of the CC family, and its gene maps to human chromosome 17q. In the mouse, only a pseudogene has been identified to date (27,28). CCL16 is a functional ligand for CCR1, CCR2, CCR5 (29), and CCR8 (30).…”

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confidence: 99%

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Intralesional Injection of Adenovirus Encoding CC Chemokine Ligand 16 Inhibits Mammary Tumor Growth and Prevents Metastatic-Induced Death after Surgical Removal of the Treated Primary Tumor

Guiducci

Carlo

Parenza

et al. 2004

The Journal of Immunology

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The CC chemokine ligand (CCL)16 exerts chemotactic activity on human monocytes and lymphocytes. Although no murine homologous has been defined, the TSA mouse adenocarcinoma cells engineered to express human CCL16 are rapidly rejected by syngenic mice. An adenovirus encoding CCL16 (AdCCL16) was generated using a Cre-Lox-based system and was used to determine whether this chemokine might also block pre-existing tumors. Both recombinant and viral CCL16 showed in vitro chemotactic activity for murine CD4+ and CD8+ lymphocytes and dendritic cells (DC). AdCCL16, but not the control empty vector, when injected in established nodules significantly delayed tumor growth. Immunohistochemistry revealed accumulation of CD4+ and CD8+ T cells and DC in the treated tumors as well as in draining lymph nodes. DC from such lymph nodes stimulated IFN-γ by a T cell clone specific for the known TSA tumor-associated Ag (TAA), suggesting the tumor origin of these cells. Lymphocytes from the same nodes showed specific CTL activity against TSA tumor cells and their immunodominant TAA peptide. Antitumor activity required CD4, CD8, and IFN-γ production, as shown using subset-depleted and knockout mice. Despite the robust and rapid immune response triggered by intratumoral injection of AdCCL16, the lesions were not completely rejected; however, the same treatment given before surgical excision of primary lesions prevented metastatic spread and cured 63% of mice bearing the 4T1 mammary adenocarcinoma, which is perhaps the most compelling model of spontaneous metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Intralesional Injection of Adenovirus Encoding CC Chemokine Ligand 16 Inhibits Mammary Tumor Growth and Prevents Metastatic-Induced Death after Surgical Removal of the Treated Primary Tumor

Guiducci

Carlo

Parenza

et al. 2004

The Journal of Immunology

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“…1 CCL16, also known as liver-expressed chemokine or NCC-4 or lymphocyte and monocyte chemoattractant or HCC-4, is a CC chemokine that specifically attracts lymphocytes, dendritic cells, and monocytes; increases their adhesive properties; and has myelosuppressive activity. [2][3][4][5][6] It is constitutively expressed in liver 3,7 and is increased by interleukin 10 (IL-10) in activated monocytes. 2 Interestingly, CCL16 is present in human plasma suggesting that it may be active outside hepatic tissue.…”

Section: Introductionmentioning

confidence: 99%

CCL16 activates an angiogenic program in vascular endothelial cells

Strasly¹

2004

Blood

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Besides regulating leukocyte trafficking in normal and injured tissues, several chemokines may positively or negatively regulate angiogenesis. Here we report that CCL16 activates an angiogenic program in vascular endothelial cells by activating CCR1. CCL16 induces dose-dependent random and directional migration of endothelial cells isolated from large vessels and liver capillaries without inducing their proliferation. It also promotes endothelial differentiation into capillary-like structures in an in vitro assay and is angiogenic in the chick chorionallantoic membrane. These angiogenic activities are neutralized by a specific antibody against CCL16. The direct angiogenic activity of CCL16 is further amplified by its ability to prime endothelium to a mitogen signal induced by vascular endothelial growth factor A and to raise their basal production of CXCL8 and CCL2, 2 other angiogenic chemokines. BX471 ( IntroductionChemokines are polypeptide molecules mainly involved in the control of leukocyte functions and trafficking through the activation of receptors belonging to the 7-transmembrane spanning, G-protein-coupled receptor family. Near the NH 2 end of the molecule, the presence of cysteine residues identifies 4 subfamilies. They are characterized by the presence of a unique C, or of 2 Cs separated by a single (CXC) or 3 amino acids (CXXXC) or adjacent (CC), and show largely overlapping biologic activities. 1 CCL16, also known as liver-expressed chemokine or NCC-4 or lymphocyte and monocyte chemoattractant or HCC-4, is a CC chemokine that specifically attracts lymphocytes, dendritic cells, and monocytes; increases their adhesive properties; and has myelosuppressive activity. [2][3][4][5][6] It is constitutively expressed in liver 3,7 and is increased by interleukin 10 (IL-10) in activated monocytes. 2 Interestingly, CCL16 is present in human plasma suggesting that it may be active outside hepatic tissue. 7 CCR1, CCR2, CCR5, and CCR8 are the functional receptors of this chemokine. 5,7 CCL16 released by engineered tumor cells elicits their rejection by a CD8 ϩ -and neutrophil-dependent mechanism and a rapid induction of a tumor-specific systemic immune response. This suggests that CCL16 improves recognition of poorly immunogenic cells by promoting a cross talk between T lymphocytes and antigenpresenting cells. 8 The histochemical analysis of these tumors showed expression of adhesion molecules by endothelial cells (ECs), without signs of vascular necrosis or inhibition of angiogenesis, in spite of the abundant neutrophil infiltrate that usually characterizes other models of tumor rejection promoted by cytokines, where vasculature is severely affected. [9][10][11][12][13] Chemokines play a role in embryo and adult vascular bed formation. 14,15 Besides an indirect mechanism involving angiogenic inducers released by activated leukocytes, 16,17 both CC and CXC chemokines may directly activate a proangiogenic [18][19][20][21][22][23][24][25][26][27][28] or an angiostatic 19,[29][30][31][32][33][34][35] program in ECs...

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“…Rejection is associated with an impressive infiltrate of macrophages, dendritic cells, T cells, and polymorphonuclear (PMN) 4 leukocytes, and is attributable to the last two populations. It is followed by the establishment of an effective and specific immune memory against TSA wild-type parental cells (TSA-pc).…”

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confidence: 99%

Tumor Rejection and Immune Memory Elicited by Locally Released LEC Chemokine Are Associated with an Impressive Recruitment of APCs, Lymphocytes, and Granulocytes

Giovarelli

Cappello

Forni

et al. 2000

The Journal of Immunology

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The human β chemokine known as LEC (also called NCC-4, HCC-4, or LMC) displays chemotactic activity for monocytes and dendritic cells. The possibility that its local presence increases tumor immunogenicity is addressed in this paper. TSA parental cells (TSA-pc) are poorly immunogenic adenocarcinoma cells that grow progressively, kill both nu/nu and syngeneic BALB/c mice, and give rise to lung metastases. TSA cells engineered to release LEC (TSA-LEC) are still able to grow in nu/nu mice, but are promptly rejected and display a marginal metastatic phenotype in BALB/c mice. Rejection is associated with a marked T lymphocyte and granulocyte infiltration, along with extensive macrophage and dendritic cell recruitment. NK cells and CD4+ T lymphocytes are uninfluential in TSA-LEC cell rejection, whereas both CD8+ lymphocytes and polymorphonuclear leukocytes play a major role. An antitumor immune memory is established very quickly after rejection, since 6 days later 75% of BALB/c mice were already resistant to a TSA-pc challenge. Spleen cells from rejecting mice display specific cytotoxic activity against TSA-pc and secrete IFN-γ and IL-2 when restimulated by TSA-pc. The ability of LEC to markedly improve recognition of poorly immunogenic cells by promoting APC-T cell cross-talk suggests that it could be an effective component of antitumor vaccines.

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Isolation of cDNA encoding a novel human CC chemokine NCC-4/LEC

Cited by 30 publications

References 19 publications

Intralesional Injection of Adenovirus Encoding CC Chemokine Ligand 16 Inhibits Mammary Tumor Growth and Prevents Metastatic-Induced Death after Surgical Removal of the Treated Primary Tumor

Intralesional Injection of Adenovirus Encoding CC Chemokine Ligand 16 Inhibits Mammary Tumor Growth and Prevents Metastatic-Induced Death after Surgical Removal of the Treated Primary Tumor

CCL16 activates an angiogenic program in vascular endothelial cells

Tumor Rejection and Immune Memory Elicited by Locally Released LEC Chemokine Are Associated with an Impressive Recruitment of APCs, Lymphocytes, and Granulocytes

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